Objectives To investigate the association between altered glucose/insulin homeostasis and ovarian dysfuntion in pre-natally androgenized female rhesus monkeys, as part of a study investigating the etiology of polycystic ovarian syndrome (PCOS). ABSTRACT:Ovulatory dysfunction is positively correlated with body mass index (BMI; weight [kg]/crown-rump length[m2]) and fasting plasma insulin levels in adult female rhesus monkeys androgenized prenatally (A), but not in controls (C). To examine the role of altered glucose/insulin homeostasis in ovulatory dysfunction, blood samples were regularly withdrawn from 13 A females and 6 C females with increased BMI (r 34 kg/m2) for 3 months. Thirty-eight percent of A females and 0% of C females were defined as anovulatory from their low serum progesterone concentrations. An intravenous frequently sampled glucose tolerance test was performed during the early follicular phase of the menstrual cycle or during the anovulatory period and analyzed by the Modified Minimal Model method of Bergman. Basal plasma glucose levels were elevated in A (61.8[57.0-67.0]mg/dl; mean[95% confidence limits]) compared to C (52.5[46.7-59.0] mg/dl, p < 0.04) females, whereas basal plasma insulin levels (33.19[20.8-53.1] vs. 41.7[30.3-57.4] U/ml) and insulin sensitivity (SI; 2.82[1.78-4.48] vs. 2.75[1.94-3.92]x10-4min-1. U-1.ml-1) were not significantly different between the two groups. Acute insulin response to glucose (AIR; 110.2[83.7-145.1] vs. 190.6 [126.9-286.0] U/ml; p<0.04), disposition index (the product of SI and AIR; 933.3[721.6-1207.0] vs. 1574.0[1082.2-2289.2]; p<0.04) and insulin response to tolbutamide (147.2[113.3-191.3] vs. 244.3[166.5-358.6] U/ml; p<0.05) were significantly lower in A females compared to C females. Prenatal androgenization of female rhesus monkeys with increased BMI is associated with reduced dynamic insulin responsiveness, elevated fasting plasma glucose levels and anovulation. Key words infertility, anovulation, adiposity, polycystic ovarian syndrome, insulin, glucose.